Biomaterial Database

Role of the carbohydrate moiety of human choriogonadotropin in its thyrotropic activity. 1984

S Amr, and Y Shimohigashi, and P Carayon, and H C Chen, and B Nisula

To investigate the role of the carbohydrate moiety of human choriogonadotropin (hCG) in its thyrotropic activity, highly purified hCG and its desialylated subunits were treated with anhydrous HF/anisole (1 h, 0 degree C). The deglycosylated alpha- and beta-subunits were recombined with their native complementary subunits, and the interactions of these hCG congeners with the thyrotropin (TSH) receptor-adenylate cyclase system were investigated using human thyroid membranes. Deglycosylated hCG (dghCG) bound to the high affinity-low capacity TSH-binding sites of thyroid membranes; its equilibrium dissociation constant was lower than that of asialo-hCG (ashCG) (ED50: 2.6 and 6 microM, respectively). Like ashCG, dghCG did not stimulate thyroidal adenylate cyclase, but rather inhibited TSH stimulation of this enzyme in a dose-dependent manner. Thus, dghCG behaved as an antagonist and exhibited an inhibition constant of 0.78 microM while ashCG exhibited a constant of 1.50 microM. As might be predicted from the behavior of dghCG, absence of carbohydrate from either subunit enhanced the ability of the hCG hybrid recombinants to interact with the TSH receptor-adenylate cyclase system. However, only the hybrid recombinant lacking carbohydrate on its alpha-subunit lacked intrinsic thyrotropic activity; the hybrid recombinant lacking carbohydrate on its beta-subunit not only displayed intrinsic thyrotropic activity, but was of even higher potency than intact hCG in stimulating thyroidal adenylate cyclase. These results demonstrate that the carbohydrate moieties of both hCG subunits impede the process of recognition of hCG by the TSH receptor, while the carbohydrate moiety of the alpha-subunit, but not that of the beta-subunit, is essential for the process of hCG activation of thyroidal adenylate cyclase.

UI	MeSH Term	Description	Entries
D009439	Neuraminidase	An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992)	Sialidase,Exo-alpha-Sialidase,N-Acylneuraminate Glycohydrolases,Oligosaccharide Sialidase,Exo alpha Sialidase,Glycohydrolases, N-Acylneuraminate,N Acylneuraminate Glycohydrolases,Sialidase, Oligosaccharide
D011956	Receptors, Cell Surface	Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.	Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D011989	Receptors, Thyrotropin	Cell surface proteins that bind pituitary THYROTROPIN (also named thyroid stimulating hormone or TSH) and trigger intracellular changes of the target cells. TSH receptors are present in the nervous system and on target cells in the thyroid gland. Autoantibodies to TSH receptors are implicated in thyroid diseases such as GRAVES DISEASE and Hashimoto disease (THYROIDITIS, AUTOIMMUNE).	Receptors, Thyroid Stimulating Hormone,TSH Receptors,Thyroid Stimulating Hormone Receptors,Thyrotropin Receptors,LATS Receptors,Receptor, LATS Immunoglobulins,Receptors, LATS,Receptors, Long-Acting Thyroid Stimulator,Receptors, TSH,TSH Receptor,Thyroid Stimulating Hormone Receptor,Thyrotropin Receptor,Receptor, TSH,Receptor, Thyrotropin,Receptors, Long Acting Thyroid Stimulator
D002241	Carbohydrates	A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. The largest class of organic compounds, including STARCH; GLYCOGEN; CELLULOSE; POLYSACCHARIDES; and simple MONOSACCHARIDES.	Carbohydrate
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002621	Chemistry	A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006063	Chorionic Gonadotropin	A gonadotropic glycoprotein hormone produced primarily by the PLACENTA. Similar to the pituitary LUTEINIZING HORMONE in structure and function, chorionic gonadotropin is involved in maintaining the CORPUS LUTEUM during pregnancy. CG consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is virtually identical to the alpha subunits of the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity (CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN).	Chorionic Gonadotropin, Human,HCG (Human Chorionic Gonadotropin),Biogonadil,Choriogonadotropin,Choriogonin,Chorulon,Gonabion,Human Chorionic Gonadotropin,Pregnyl,Gonadotropin, Chorionic,Gonadotropin, Human Chorionic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006858	Hydrofluoric Acid	Hydrofluoric acid. A solution of hydrogen fluoride in water. It is a colorless fuming liquid which can cause painful burns.	Hydrogen Fluoride,Fluohydric Acid,Fluorhydric Acid,Acid, Fluohydric,Acid, Fluorhydric,Acid, Hydrofluoric,Fluoride, Hydrogen